He was knighted in Queen Victoria's Diamond Jubilee year Honours in 1897. The Jewish Chronicle of that time noted "a Russian Jew, trained in the schools of European science, saves the lives of helpless Hindoos and Mohammedans and is decorated by the descendant of William the Conqueror and Alfred the Great" (Page 8 of the London Jewish Chronicle 1 June 2012).

Young Haffkine was also a member of the Jewish League for Self-Defense. Haffkine was injured while defending a Jewish home during a pogrom. As a result of this action he was arrested but later released due to the intervention of Ilya Mechnikov.

Haffkine continued his studies with famous biologist Ilya Mechnikov, but after the assassination of TsarAlexander II, the government increasingly cracked down on people it considered suspicious, including intelligentsia. Mechnikov left the country for Pasteur Institute in Paris.[2]

The euglenidgenusKhawkinea is named in honor of Haffkine's early studies of euglenids, first published in French journals with the author name translated from cyrillic as "Mardochée-Woldemar Khawkine".

Haffkine focused his research on developing cholera vaccine and produced an attenuated form of the bacterium. Risking his own life, on July 18, 1892, Haffkine performed the first human test on himself and reported his findings on July 30 to the Biological Society. Even though his discovery caused an enthusiastic stir in the press, it was not widely accepted by his senior colleagues, including both Mechnikov and Pasteur, nor by European official medical establishment in France, Germany and Russia.

The scientist decided to move to India where hundreds of thousands died from ongoing epidemics.[2] At first, he was met with deep suspicion and survived an assassination attempt by Islamic extremists during the first year there (1893), but he managed to vaccinate about 25,000 volunteers, most of whom survived.[5] After contracting malaria, Haffkine had to return to France.

In his August 1895 report to Royal College of Physicians in London about the results of his Indian expedition, Haffkine dedicated his successes to Pasteur, who recently had died. In March 1896, against his doctor's advice, Haffkine returned to India and performed 30,000 vaccinations in seven months.

"Unlike tetanus or diphtheria, which were quickly neutralized by effective vaccines by the 1920's, the immunological aspects of bubonic plague proved to be much more daunting."[6] In October 1896, an epidemic of bubonic plague struck Mumbai and the government asked Haffkine to help. He embarked upon the development of a vaccine in a makeshift laboratory in a corridor of Grant Medical College. In three months of persistent work (one of his assistants experienced a nervous breakdown, two others quit), a form for human trials was ready and on January 10, 1897[7] Haffkine tested it on himself. "Haffkine's vaccine used a small amount of the bacteria to produce an immune reaction."[8] After these results were announced to the authorities, volunteers at the Byculla jail were inoculated and survived the epidemics, while seven inmates of the control group died. "Like others of these early vaccines, the Haffkine formulation had nasty side effects, and did not provide complete protection, though it was said to have reduced risk by up to 50 percent."[6][8]

Haffkine's successes in fighting the ongoing epidemics were indisputable, but some officials still insisted on old methods based on sanitarianism: washing homes by fire hose with lime, herding affected and suspected persons into camps and hospitals, and restricting travel.

Even though the official Russia was still unsympathetic to his research, Haffkine's Russian colleagues doctors V.K. Vysokovich and D.K. Zabolotny visited him in Bombay. During the 1898 cholera outbreak in the Russian Empire, the vaccine called "лимфа Хавкина" ("limfa Havkina", Havkin's lymph) saved thousands of lives across the empire.

By the turn of the 20th century, the number of inoculees in India alone reached four million and doctor Haffkine was appointed the Director of the Plague Laboratory in Mumbai (now called Haffkine Institute).[2]

Haffkine was the first to prepare a vaccine for human prophylaxis by killing virulent culture by heat at 60 °C.[9] The major limit of his vaccine was the lack of activity against pulmonary forms of plague.[10]

In 1898, Haffkine approached Aga Khan III with an offer for SultanAbdul Hamid II to resettle Jews in Palestine, then a province of the Ottoman Empire: the effort "could be progressively undertaken in the Holy Land", "the land would be obtained by purchase from the Sultan's subjects", "the capital was to be provided by wealthier members of the Jewish community", but the plan was rejected.

In 1902, nineteen Indian villagers (inoculated from a single bottle of vaccine) died of tetanus. An inquiry commission indicted Haffkine, and he was relieved of his position and returned to England. The report was unofficially known as "Little Dreyfus affair", as a reminder of Haffkine's Jewish background and religion.

The Lister Institute reinvestigated the claim and overruled the verdict: it was discovered that an assistant used a dirty bottle cap without sterilizing it.

Published materials from the India Home Department related to the vaccination incident (along with Haffkine's personal diaries on microfilm) are held at the National Library of Medicine in Bethesda, Maryland.[12]

Since Haffkine's post in Mumbai was already occupied, he moved to Calcutta and worked there until his retirement in 1914. Professor Haffkine returned to France and later moved to Lausanne, where he spent the last years of his life. During his brief visit to the Soviet Union in 1927, he found drastic changes in the country of his birth.

Haffkine received numerous honors and awards. In 1925, the Plague Laboratory in Mumbai, Maharashtra was renamed the Haffkine Institute. In commemoration of the centennial of his birth, Haffkine Park was planted in Israel in 1960s.

In an autobiography of him, Nobelist Selman Abraham Waksman explains that, in this last phase of his life, Haffkine had became a deeply religious man. Haffkine returned to Orthodox Jewish practice and wrote A Plea for Orthodoxy (1916). In this article, he advocated traditional religious observance and decried the lack of such observance among "enlightened" Jews, and stressed the importance of community life, stating:

A brotherhood built up of racial ties, long tradition, common suffering, faith and hope, is a long tradition, common suffering, faith and hope, is a union ready-made, differing from artificial unions in that the bonds existing between the members contain an added promise of duration and utility. Such a union takes many centuries to form and is a power for good, the neglect or disuse of which is as much an injury to humanity as the removal of an important limb is to the individual... no law of nature operates with more fatality and precision than the law according to which those communities survive in the strife for existence that conform the nearest to the Jewish teachings on the relation of man to his Creator; on the ordering of time for work and rest; on the formation of families and the duties of husband and wife, parents and children ; on the paramount obligations of truthfulness and justice between neighbor and neighbor and to the stranger within the gates.

In addition, in 1929, he established the Haffkine Foundation to foster Jewish education in Eastern Europe. Haffkine was also profoundly respectful of other religions, and "he considered it of the utmost importance to promote the study of the Bible."[14]